Amplification of PVT1 contributes to the pathophysiology ofovarian and breast cancer

Journal Article · Tue Oct 09 04:00:00 EDT 2007 · Clinical Cancer Research

DOI:https://doi.org/10.1158/1078-0432.CCR-06-2882· OSTI ID:918822

Guan, Yinghui; Kuo, Wen-Lin; Stilwell, Jackie; Takano, Hirokuni; Lapuk, Anna; Fridlyand, Jane; Mao, Jian-Hua; Yu, Mami; Ginzinger, David; Gray, Joe W

Purpose. This study was designed to elucidate the role of amplification at 8q24 in the pathophysiology of ovarian and breast cancer since increased copy number at this locus is one of the most frequent genomic abnormalities in these cancers. Experimental Design. To accomplish this, we assessed the association of amplification at 8q24 with outcome in ovarian cancers using FISH to tissue microarrays and measured responses of ovarian and breast cancer cell lines to specific small interfering RNAs (siRNA) against the oncogene, MYC, and a putative noncoding RNA, PVT1, both of which map to 8q24. Results. Amplification of 8q24 was associated with significantly reduced survival duration. In addition, siRNA-mediated reduction in either PVT1 or MYC expression inhibited proliferation in breast and ovarian cancer cell lines in which they were both amplified and over expressed but not in lines in which they were not amplified/over expressed. Inhibition of PVT1 expression also induced a strong apoptotic response in cell lines in which it was over expressed but not in lines in which it was not amplified/over expressed. Inhibition of MYC, on the other hand, did not induce an apoptotic response in cell lines in which MYC was amplified and over expressed. Conclusions. These results suggest that MYC and PVT1 contribute independently to ovarian and breast pathogenesis when over expressed because of genomic abnormalities. They also suggest that PVT1 mediated inhibition of apoptosis may explain why amplification of 8q24 is associated with reduced survival duration in patients treated with agents that act through apoptotic mechanisms.

• Research Organization: Ernest Orlando Lawrence Berkeley NationalLaboratory, Berkeley, CA (US)
• Sponsoring Organization: USDOE Director. Office of Science. Biological andEnvironmental Research
• DOE Contract Number: AC02-05CH11231
• OSTI ID: 918822
• Report Number(s): LBNL--62043; BnR: KP1104010
• Journal Information: Clinical Cancer Research, Journal Name: Clinical Cancer Research Journal Issue: 19 Vol. 13
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
AMPLIFICATION
APOPTOSIS
MAMMARY GLANDS
NEOPLASMS
OVARIES
PATHOGENESIS
PATIENTS
PROLIFERATION
RNA